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1.
Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors 总被引:116,自引:0,他引:116
Yamashita J Itoh H Hirashima M Ogawa M Nishikawa S Yurugi T Naito M Nakao K Nishikawa S 《Nature》2000,408(6808):92-96
Interaction between endothelial cells and mural cells (pericytes and vascular smooth muscle) is essential for vascular development and maintenance. Endothelial cells arise from Flk1-expressing (Flk1+) mesoderm cells, whereas mural cells are believed to derive from mesoderm, neural crest or epicardial cells and migrate to form the vessel wall. Difficulty in preparing pure populations of these lineages has hampered dissection of the mechanisms underlying vascular formation. Here we show that Flk1+ cells derived from embryonic stem cells can differentiate into both endothelial and mural cells and can reproduce the vascular organization process. Vascular endothelial growth factor promotes endothelial cell differentiation, whereas mural cells are induced by platelet-derived growth factor-BB. Vascular cells derived from Flk1+ cells can organize into vessel-like structures consisting of endothelial tubes supported by mural cells in three-dimensional culture. Injection of Flk1+ cells into chick embryos showed that they can incorporate as endothelial and mural cells and contribute to the developing vasculature in vivo. Our findings indicate that Flk1+ cells can act as 'vascular progenitor cells' to form mature vessels and thus offer potential for tissue engineering of the vascular system. 相似文献
2.
Construction of chimaeric processed immunoglobulin genes containing mouse variable and human constant region sequences 总被引:3,自引:0,他引:3
The specificity of monoclonal antibodies provides a powerful diagnostic and therapeutic tool in investigating human neoplasia. Radiological scanning and immunotherapy with mouse tumour-specific monoclonal antibodies have been applied to patients with some success, but a major problem is the neutralization of the mouse antibody induced by repeated administration of heterologous antibodies. To avoid or reduce such immune reactions, chimaeric immunoglobulins consisting of mouse variable (V) and human constant (C) regions can be synthesized. We have constructed a recombinant retrovirus DNA carrying genomic heavy-chain (H) variable-diversity joining (VH-D-JH) and C gamma 1 genes from different species and show here that the chimaeric intervening sequences are spliced out precisely. This procedure provides a useful method to construct the chimaeric mouse-human immunoglobulin gene to be expressed in Escherichia coli, yeast and animal cells. Unexpectedly, a hidden splice donor site in the 5'-flanking region of a human VH gene is used in place of the donor site of the leader sequence exon, resulting in the formation of the V region without the leader sequence. 相似文献
3.
Y. Kawamoto T. Hanaichi M. Naito A. Miyama 《Cellular and molecular life sciences : CMLS》1990,46(5):495-498
Summary Human myocardial cells from fresh autopsy material contained granules which possessed hemolytic activity against guinea pig and rabbit erythrocytes. The hemolytic granules, which had a density of 1.02 and a diameter of 200–300 nm, were recovered as a microsome fraction from subcellular homogenates of human myocardial cells by differential centrifugation in 300 mM sucrose containing 0.1 mM PMSF and 10 mM EDTA. The membrane lesions caused by the granules were ring-like structures with an internal diameter of about 10–17 nm, analogous to that caused by perforin- and complement-induced lysis. However, the requirement for divalent cation differed from that for perforin-induced lysis, since the microsome-mediated lysis occurred in the presence of EDTA. 相似文献
4.
The ground state of superconductors is characterized by the long-range order of condensed Cooper pairs: this is the only order present in conventional superconductors. The high-transition-temperature (high-T(c)) superconductors, in contrast, exhibit more complex phase behaviour, which might indicate the presence of other competing ground states. For example, the pseudogap--a suppression of the accessible electronic states at the Fermi level in the normal state of high-T(c) superconductors-has been interpreted as either a precursor to superconductivity or as tracer of a nearby ground state that can be separated from the superconducting state by a quantum critical point. Here we report the existence of a second order parameter hidden within the superconducting phase of the underdoped (electron-doped) high-T(c) superconductor Pr2-xCe(x)CuO4-y and the newly synthesized electron-doped material La2-xCe(x)CuO4-y (ref. 8). The existence of a pseudogap when superconductivity is suppressed excludes precursor superconductivity as its origin. Our observation is consistent with the presence of a (quantum) phase transition at T = 0, which may be a key to understanding high-T(c) superconductivity. This supports the picture that the physics of high-T(c) superconductors is determined by the interplay between competing and coexisting ground states. 相似文献
5.
Yutaka Naito Yusuke Yoshioka Yusuke Yamamoto Takahiro Ochiya 《Cellular and molecular life sciences : CMLS》2017,74(4):697-713
Intercellular communication plays an important role in cancer initiation and progression through secretory molecules, including growth factors and cytokines. Recent advances have revealed that small membrane vesicles, termed extracellular vesicles (EVs), served as a regulatory agent in the intercellular communication of cancer. EVs enable the transfer of functional molecules, including proteins, mRNA and microRNAs (miRNAs), into recipient cells. Cancer cells utilize EVs to dictate the unique phenotype of surrounding cells, thereby promoting cancer progression. Against such “education” by cancer cells, non-tumoral cells suppress cancer initiation and progression via EVs. Therefore, researchers consider EVs to be important cues to clarify the molecular mechanisms of cancer biology. Understanding the functions of EVs in cancer progression is an important aspect of cancer biology that has not been previously elucidated. In this review, we summarize experimental data that indicate the pivotal roles of EVs in cancer progression. 相似文献
6.
Takeaki Naito 《复旦学报(自然科学版)》2005,44(5):758-759
1 Introduction Strategies involving radical reactions have become preeminent tools in organic synthesis. Free radical-mediated cyclization has developed as a powerful method for preparing various types of cyclic compounds via carbon-carbon bond-forming processes. In order to develop effective and convenient methods for the synthesis of biologically active cyclic amines, we have focused our efforts on radical reactions using aldehydes, ketones, and C-C multiple bonds as a radical precursor and… 相似文献
7.
Human myocardial cells from fresh autopsy material contained granules which possessed hemolytic activity against guinea pig and rabbit erythrocytes. The hemolytic granules, which had a density of 1.02 and a diameter of 200-300 nm, were recovered as a microsome fraction from subcellular homogenates of human myocardial cells by differential centrifugation in 300 mM sucrose containing 0.1 mM PMSF and 10 mM EDTA. The membrane lesions caused by the granules were ring-like structures with an internal diameter of about 10-17 nm, analogous to that caused by perforin- and complement-induced lysis. However, the requirement for divalent cation differed from that for perforin-induced lysis, since the microsome-mediated lysis occurred in the presence of EDTA. 相似文献
8.
Enomoto R Tanimori T Naito T Yoshida T Yanagita S Mori M Edwards PG Asahara A Bicknell GV Gunji S Hara S Hara T Hayashi S Itoh C Kabuki S Kajino F Katagiri H Kataoka J Kawachi A Kifune T Kubo H Kushida J Maeda S Maeshiro A Matsubara Y Mizumoto Y Moriya M Muraishi H Muraki Y Nakase T Nishijima K Ohishi M Okumura K Patterson JR Sakurazawa K Suzuki R Swaby DL Takano K Takano T Tokanai F Tsuchiya K Tsunoo H Uruma K Watanabe A Yoshikoshi T 《Nature》2002,416(6883):823-826
Protons with energies up to approximately 10(15) eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (pi(0)), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in gamma-rays with a particular spectral-energy distribution. Here we report the observation of cascade showers of optical photons resulting from gamma-rays at energies of approximately 10(12) eV hitting Earth's upper atmosphere, in the direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match to that predicted by pion decay, and cannot be explained by other mechanisms. 相似文献
9.
Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter 总被引:71,自引:0,他引:71
Y Noma P Sideras T Naito S Bergstedt-Lindquist C Azuma E Severinson T Tanabe T Kinashi F Matsuda Y Yaoita 《Nature》1986,319(6055):640-646
Complementary DNA encoding the IgG1 induction factor, the first lymphokine directed to B lymphocytes, from a murine T-cell line has been cloned using a new strategy. The putative primary amino-acid sequence was deduced from the nucleotide sequence determined. The lymphokine synthesized by the direction of this cloned cDNA has many other functions, such as production of B-cell growth factor-1 and induction of Ia on B cells. 相似文献
10.
Zhu W Shiojima I Ito Y Li Z Ikeda H Yoshida M Naito AT Nishi J Ueno H Umezawa A Minamino T Nagai T Kikuchi A Asashima M Komuro I 《Nature》2008,454(7202):345-349
Insulin-like growth-factor-binding proteins (IGFBPs) bind to and modulate the actions of insulin-like growth factors (IGFs). Although some of the actions of IGFBPs have been reported to be independent of IGFs, the precise mechanisms of IGF-independent actions of IGFBPs are largely unknown. Here we report a previously unknown function for IGFBP-4 as a cardiogenic growth factor. IGFBP-4 enhanced cardiomyocyte differentiation in vitro, and knockdown of Igfbp4 attenuated cardiomyogenesis both in vitro and in vivo. The cardiogenic effect of IGFBP-4 was independent of its IGF-binding activity but was mediated by the inhibitory effect on canonical Wnt signalling. IGFBP-4 physically interacted with a Wnt receptor, Frizzled 8 (Frz8), and a Wnt co-receptor, low-density lipoprotein receptor-related protein 6 (LRP6), and inhibited the binding of Wnt3A to Frz8 and LRP6. Although IGF-independent, the cardiogenic effect of IGFBP-4 was attenuated by IGFs through IGFBP-4 sequestration. IGFBP-4 is therefore an inhibitor of the canonical Wnt signalling required for cardiogenesis and provides a molecular link between IGF signalling and Wnt signalling. 相似文献